Targeting Sestrin2 Impairs Survival Of Senescent Cancer Cells Following DNA-Damaging Therapies
Many common cancer treatments, like chemotherapy and radiation, work by damaging the DNA of cancer cells, stopping them from growing. However, these therapies often leave behind a population of “senescent” cells. Think of these as zombie-like cells: they stop dividing, but they don’t die. Instead, they linger, releasing signals that can actually promote tumor regrowth and resistance to further treatment.
Recent research has shed light on a crucial player in the survival of these stubborn senescent cancer cells: a protein called Sestrin2. Scientists discovered that Sestrin2 becomes highly active in these senescent cells after DNA-damaging therapies. When Sestrin2 is blocked or removed, it specifically harms these senescent cancer cells, while leaving healthy, dividing cells unaffected.
The mechanism behind this is fascinating. Without Sestrin2, the senescent cells experience increased “endoplasmic reticulum (ER) stress,” which is like a cellular alarm system going off. This stress, combined with an amplification of certain cellular signals (known as SASP gene expression and NF-κB activation), triggers the cells to undergo “programmed cell death,” essentially causing them to self-destruct. This targeted elimination of senescent cells could be a game-changer, offering a new strategy to improve the effectiveness of existing cancer treatments, potentially preventing cancer recurrence and overcoming treatment resistance.
Source: link to paper